Smith Magenis Syndrome Study (SMS)

Smith Magenis Syndrome (SMS) is a complex disorder characterized by severe neurological, psychological and behavioral disorders including sleep-wake rhythm disorders. It is a rare disease with a prevalence of 1/25 000. The sleep disorders observed could be the consequence of a general dysregulation of the circadian system, since these patients show an inversion of the melatonin secretion profile. In SMS, the peak of melatonin is observed at 12 o'clock, whereas it is nocturnal in healthy subjects (3-4 o'clock in the morning). Daylight plays a important role in circadian regulation by inducing an inhibition of melatonin secretion via the suprachiasmatic nuclei of the hypothalamus. This mechanism could be affected in SMS children, explaining the lag of melatonin profile. These sleep-wake disturbances cycle could play a significant role in learning deficits and in the frequency and severity of behavioral abnormalities observed in SMS. In this project, investigators propose to study the mechanisms involved in the sleep-wake cycle disorders observed in Smith Magenis children, in particular by evaluating the quality of the pupillary reflex using a pupillometer. The pupillary reflex is a simple and non-invasive method to test light sensitivity and the photobiological mechanisms involved. In this way, investigators want to evaluate the diurnal profile of the pupillary reflex in children with Smith Magenis syndrome in relation to the diurnal melatonin profile. Investigators will complete this study by determining the chronobiological profile of Smith Magenis patients by measuring different variables: Diurnal cortisol and amylase profile 24h body temperature and heart rate profile Urinary cortisol and 6-sulfatoxymelatonin (major metabolite of melatonin) profiles Daytime sleepiness profile measured subjectively by questionnaire and objectively via a waking EEG recording. Actimetry at home Polysomnography A neurocognitive and behavioural assessment

Sleep disorders, Chronobiology, Smith Magenis Syndrome, Paediatrics, Pupillary reflex, Circadian rhythm, Melatonin

Measurement of the percentage change between pupil diameter at the end of light exposure and before exposure

This measurement will allow to evaluate the diurnal profile of the pupillary reflex and will be measured by a NeuroLight pupillometer (IDMed). This measurement will be done every 2 hours from 8am to 8pm, for one day

This measurement will allow to evaluate the diurnal melatonin profile and will be evaluated using saliva samples. This measurement will be done every 2 hours from 8am to 8pm, for one day

Determination of the chronobiological profile : Assessment of sleepiness by questionnaire (numerical score)

The Karolinska questionnaire will be carried out at the time of salivary sampling and pupil diameter measurement and the score obtained will be compared with the salivary melatonin level.

Home activity monitor during an outpatient recording with a watch in order to assess the sleep wake rhythm at home

Inclusion Criteria: Genetically confirmed Smith Magenis syndrome (microdeletion of the short arm of chromosome 17 or mutation of the RAI1 gene; obtained by FISH, CGH-array or molecular biology) Aged 7-12 years Consent form signed by the parent(s) Requiring a sleep assessment in the Hopital Femme Mère Enfant paediatric sleep unit of Pr Franco Affiliation to a social security system. Exclusion Criteria: Associated ophthalmological disorders that do not allow the photomotor reflex to be studied: optic neuritis, glaucoma and retinitis pigmentosa. Dyschromatopsia detected in consultation with a rapid Ishihara test adapted to the child's cognitive level, if necessary supplemented by a test performed by ophthalmologists. Algic child (risk of measurement bias: when a patient is in pain his pupils dilate and we observe a greater amplitude in the photomotor reflex), defined by a score on the FPS-R Face Scale >4/10.

Service Épilepsie-Sommeil-Explorations Fonctionnelles Neurologiques Pédiatriques Hôpital Femme-Mère-Enfant HCL

GénoPsy, Reference Center for Diagnosis and Management of Genetic Psychiatric Disorders, Centre Hospitalier le Vinatier and EDR-Psy Q19 Team (Centre National de la Recherche Scientifique & Lyon 1 Claude Bernard University)